The objective of the research is to obtain a detailed understanding of the synaptic pharmacology of norepinephrine, dopamine and serotonin in the mammalian center nervous system (CNS). Access to this program will be achieved by electrophysiological and histochemical study of dissociated mammalian neurons in vitro. Cells dissociated from the mammalian CNS and matured in surface culture show abundant evidence of functional differentiation and offer unique advantages in terms of visualization and control of the extracellular medium. It will be possible to discriminate and characterize the actions of the monoamines on pre- and postsynaptic elements. Evidence of uniformity or diversity of synaptic mechanisms will be sought by exploring cultures derived from fetal spinal cord, brain stem, cerebellum and cerebrum. Co-cultures will be made of brain stem explants together with dissociated neurons for the purpose of evaluating monoamine and drug actions in the presence of monoaminergic innervation. The interaction of representative psychoactive drugs (initially amphetamine and flupenthioxol) with monoamine mechanisms will be analyzed at the level of the neuronal membrane. This detailed new information on the cellular mechanisms of action of the monoamines and psychoactive drugs will be of fundamental value in the study of function and dysfunction in the mammalian CNS.